This project is concerned with the biochemical and physiological roles of copper and zinc and with the interaction of these metallic ions as nutrients and enzyme cofactors. Deficiencies of copper and zinc in animals have been shown to produced pathologies simulating human disease. For example, copper deficiency produces vascular defects resulting in dissecting aneurysms and angiorhexis. This has been traced to a lack of active lysyl oxidase, a copper dependent enzyme. Lysyl oxidase is primarily responsible for the reactions leading to crosslinking and maturation of collagen and elastin. Copper deficiency also causes neurological disorders in neonatal rats and this relates to a decreased concentration of dopamine and norepinephrine in the brain tissue. A low concentration of dopamine in the corpus striatum is analogous to the condition in Parkinson's disease. These same animals show an abnormal lung morphology simulating that of developmental pulmonary emphysema. The condition is not reversible by copper administrations, but supplemented animals may serve as a useful physiological model to study emphysema. The objectives of the proposal is to use these models to study the biochemical defects involved in the pathology which relates to human disease.